Mouse treatment


The effects of experimental treatments and genetic interventions (gene knockout) on the course of infection and pathology in murine malaria models are listed in this part of the database. For each molecule, data about the genetic background of the mouse strain (and number of backcrosses), parasite species, inoculum size (pRBC), details of the treatment/knockout, effect on parasitemia, pathology and survival, additional data of the effects of the treatments (e.g. on expression of other factors), references (Refs), and a hyperlink to the original paper in the PubMed database (U.S. National Library of Medicine, National Institutes of Health) is included.

Dynamic fields: these are the columns that you can select to show in the output table. See also "How to use MalarImDB?" for more information.

Abbreviations: ALI, acute lung injury; anti-…; treatment with depleting antibodies; CM, experimental cerebral malaria (when indicated the incidence is included between brackets, e.g. CM (100%) means that 100% of the mice suffered from cerebral pathology); EG, experimental group; HP&A, hyperparasitemia and anemia; i.p., intraperitoneal administration; MA-ARDS, malaria-associated acute respiratory distress syndrome; N.I., not indicated; p.o., oral administration; r, recombinant; R, receptor; s, soluble; male mice; female mice; -/-, gene knockout mice; +, and/positive (example1: rIL-1a + anti-IFN-g: mice were treated with recombinant IL-1a and antibodies to deplete IFN-g; example2: CD4+ T cells, CD4 positive T cells); ↑, increased; ↓, decreased; ~, on average

 

SelectField
Full
Molecular group
Molecule/Cell
Plasmodium strain
pRBC infection titer
Mouse genetic background (Con)
Level of backcrossing
Experimental treatment group (EG)
Lethal infection (Con)
Lethal infection (EG)
Pathology (Con)
Pathology (EG)
Parasitemia (EG vs Con)
Additional phenotypes (EG vs Con)
Refs
PubMed
Execute an advanced search by using AND or OR between terms
Full Molecule/Cell Plasmodium strain Mouse genetic background (Con) Experimental treatment group (EG) Lethal infection (Con) Lethal infection (EG) Pathology (Con) Pathology (EG) Parasitemia (EG vs Con) Additional phenotypes (EG vs Con) Refs PubMed
CD4/CD8 Plasmodium chabaudi chabaudi AS C57BL/6 anti-CD4 and anti-CD8 no no N.I. N.I. Increased peak and developed a high, persistent parasitemia Similar parasite-specific IgM early during infection and no IgG Süss et al., 1988, Infect Immun
CD4/CD8 Plasmodium yoelii 17XNL CBA/CaJ anti-CD4 + adoptive transfer of immune CD8+ splenocytes no yes N.I. N.I. No parasite clearance N.I. Vinetz et al., 1990, J Immunol
CD4/CD8/B cells Plasmodium yoelii 17XNL CBA/CaJ anti-CD4 + adoptive transfer of immune CD8+ and B+ splenocytes no yes N.I. N.I. No parasite clearance N.I. Vinetz et al., 1990, J Immunol
CD40 Plasmodium berghei ANKA C57BL/6 CD40 -/- yes no (at the end of observation day 12) CM (100%) No CM Similar Prolonged survival (›day 12); ↓ thrombocytopenia and hypothermia; Brain: ↓ macrophage sequestration; no edema; ↑ TNF-a and ↓ ICAM-1 mRNA expression; Lung: ↓ macrophage sequestration; similar sequestration of pRBCs, PMNs and platelets; no edema; % pRBCs alveolar capillaries › % pRBCs in large blood vessels (similar to WT); ↑ TNF-a and ↓ ICAM-1; Spleen: similar splenomegaly, TNF-a and ↓ ICAM-1 mRNA expression Piguet et al., 2001, Am J Pathol
CD40L Plasmodium berghei ANKA C57BL/6 CD40L -/- yes no (at the end of observation day 12) CM (100%) No CM Similar Prolonged survival (›day 12); ↓ thrombocytopenia and hypothermia; Brain: ↓ macrophage sequestration; ↓ TNF-a and ICAM-1 mRNA expression; ↑ TNF-a and ICAM-1 mRNA expression; Spleen: ↓ splenomegaly; ↑ TNF-a and ICAM-1 mRNA expression Piguet et al., 2001, Am J Pathol
CD40L Plasmodium berghei ANKA C57BL/6J anti-CD40L yes N.I. CM (100%) N.I. Similar ↓ thrombocytopenia and hypothermia; some mice had ↓ macrophage sequestration in brain whereas other mice had ↑ macrophage and lymphocyte sequestration Piguet et al., 2001, Am J Pathol
CD40L Plasmodium berghei ANKA C57BL/6J anti-CD40L N.I. N.I. N.I. N.I. N.I. ↓ thrombocytopenia and ↓ microparticles in plasma Piguet et al., 2002, Apoptosis
CD41/CD61 (gpIIb/IIIa) Plasmodium berghei ANKA C57BL/6 anti-CD41 (early treatment) yes 9% (at the end of observation day 12) CM (100%) CM (9%) Similar Prolonged survival; ↓ CD41+ platelets in circulation Sun et al., 2003, Infect Immun
CD41/CD61 (gpIIb/IIIa) Plasmodium berghei ANKA C57BL/6 anti-CD41 (early treatment) yes 12,5% (at the end of observation day 14) CM (100%) CM (12,5%) Similar Prolonged survival (not with late treatment); ↓ CD41+CD61+, CD41-CD61+ and similar CD41-CD61- platelets in circulation; ↑ plasma IL-10, IL-1a, IL-6, IFN-g, TNF-a, fibrinogen,↓ plasma IL-2 and similar plasma factor VII, TF and vWF Van der Heyde et al., 2005, Blood
CD41/CD61 (gpIIb/IIIa) Plasmodium berghei ANKA C57BL/6 anti-CD61 (early treatment) yes 60% (at the end of observation day 14) CM (100%) CM (60%) Similar ↓ CD41+CD61+, CD41+CD61- and similar CD41-CD61- platelets in circulation Van der Heyde et al., 2005, Blood
CD54 (ICAM-1) Plasmodium berghei ANKA CBA/Ca anti-ICAM-1 yes yes CM (100%) CM (100%) Similar N.I. Falanga et al., 1991, Eur J Immunol
CD54 (ICAM-1) Plasmodium berghei ANKA C57BL/6 ICAM-1-/- yes yes CM (100%) CM (20%) Similar Prolonged survival (1-3 weeks); no neurologic symptoms; ↑ blood leukocytes and ↓ thrombocytopenia; ↓ serum TNF-a, similar serum IFN-g and NO3-; ↑ TNF-a mRNA expression in brain, similar TNF-a mRNA expression in lungs and spleen; similar VCAM expression in brain capillaries; similar macrophage accumulation in brain; ↓ macrophage, pRBC and similar PMN, platelet accumulation in lung Favre et al., 1999, Microbes Infect
CD54 (ICAM-1) Plasmodium berghei ANKA CBA/Ca anti-ICAM-1 yes yes CM (100%) Toxicity or CM Similar Earlier death (hours after antibody injection) Grau et al., 1991, Eur J Immunol
CD54 (ICAM-1) Plasmodium berghei ANKA CBA/Ca soluble ICAM-1 yes yes CM (100%) CM (100%) Similar Prolonged survival (days) Grau et al., 1991, Eur J Immunol
CD54 (ICAM-1) Plasmodium berghei ANKA C57BL/6 ICAM-1-/- yes 33% (at the end of observation day 14) CM (100%) CM (33%) Similar Prolonged survival (1-3 weeks); similar leukocyte rolling and adhesion in brain microvasculature; Li et al., 2003, J Investig Med
CD54 (ICAM-1) Plasmodium berghei ANKA C57BL/6 ICAM-1-/- N.I. N.I. N.I. N.I. N.I. % pRBCs alveolar capillaries = % pRBCs in large blood vessels of lung (in contrast to WT) Piguet et al., 2001, Am J Pathol
CD54 (ICAM-1) Plasmodium berghei ANKA C57BL/6 ICAM-1-/- N.I. N.I. N.I. N.I. N.I. ↓ platelet rolling and adhesion in brain microvasculature Sun et al., 2003, Infect Immun
CD62L (L-selectin, LECAM-1) Plasmodium berghei ANKA CBA/Ca anti-L-selectin yes yes CM (100%) CM (100%) Similar N.I. Falanga et al., 1991, Eur J Immunol
CD62P (P-selectin) Plasmodium berghei ANKA C57BL/6 P-selectin -/- yes 80% (at the end of observation day 14) CM (100%) CM (80%) Similar Prolonged survival (days); ↓leukocyte rolling and similar adhesion on the brain endothelium (also in uninfected P-selectin deficient mice compared to uninfected WT mice) Chang et al., 2003, Infect Immun
CD62P (P-selectin) Plasmodium berghei ANKA C57BL/6 x 129/Sv P-selectin -/- yes yes CM (80%) CM (4.5 %) Similar Prolonged survival (2-3 weeks); no neurological symptoms; similar platelet and leukocyte sequestration in brain vessels; chimeric mice lacking endothelial P-selectin were protected whereas chimeric mice lacking platelet P-selectin showed symptoms of CM (57.1 %) Combes et al., 2004, Am J Pathol
CD62P (P-selectin) Plasmodium berghei ANKA CBA/J anti-P-selectin yes yes CM (90%) CM (90%) Similar N.I. Combes et al., 2004, Am J Pathol
CD62P (P-selectin) Plasmodium berghei ANKA C57BL/6 P-selectin -/- N.I. N.I. N.I. N.I. N.I. Similar thrombocytopenia Sun et al., 2003, Infect Immun
CD8 Plasmodium berghei ANKA C57BL/6J anti-CD8 yes yes CM (100%) No CM Similar Prolonged survival (1-2 weeks); both early and late (prior to the onset of neurological symptoms) treatment inhibited CM Beghdadi et al., 2008, J Exp Med
CD8 Plasmodium berghei ANKA C57BL/6J anti-CD8 (late treatment) yes yes CM (100%) No CM N.I. Prolonged survival (1-2 weeks) Belnoue et al., 2003, Infect Immun
CD8 Plasmodium berghei ANKA 129P2Sv/Ev anti-CD8 (late treatment) yes yes CM (60-100%) No CM N.I. N.I. Belnoue et al., 2008, Parasite Immunol.
CD8 Plasmodium berghei ANKA 129/Sv x C57BL/6 CD8 -/- yes yes CM (53%) No CM N.I. N.I. Boubou et al., 1999, Int Immunol
CD8 Plasmodium berghei ANKA C57BL/6 anti-CD8 yes yes CM No CM Similar ↓ Evans Blue leakage in brain, lungs, kidneys and heart; ↓ edema in brain, lungs and kidneys; no cracked skull; ↓ serum lactate, HCO3- and glutamate (similar to uninfected mice); ↑ blood pH (similar to normal); similar mean arterial blood flow; ↑ cardiac output (similar to uninfected mice) Chang et al., 2001, Infect Immun
CD8 Plasmodium berghei ANKA C57BL/6J anti-CD8 yes yes CM (100%) No CM Delayed Prolonged survival (1-2 weeks); both early and late (prior to the onset of neurological symptoms) treatment inhibited CM; no neurological or respiratory symptoms Egima et al., 2007, Malar J
CD8 Plasmodium berghei ANKA C57BL/6J anti-CD8 (early treatment) yes yes CM (94%) No CM Similar Prolonged survival (1-2 weeks); both early and late (prior to the onset of neurological symptoms) treatment inhibited CM Hermsen et al., 1997, Parasitology
CD8 Plasmodium berghei ANKA C57BL/6 anti-CD8 yes yes CM (80%) No CM Transiently decreased 72 h post treatment Prolonged survival (1-2 weeks) when treated on the onset of CM; temporary improvement of clinical score; ↓ sequestration of pRBC that are transgenic for a luciferase gene Randall et al., 2008, Infect Immun
CD8 Plasmodium berghei ANKA CBA anti-CD8 yes yes CM (100%) CM (30%) Similar Prolonged survival (1-2 weeks) when treated on the onset of CM; stabilization of clinical score; ↓ sequestration of pRBC that are transgenic for a luciferase gene Randall et al., 2008, Infect Immun
CD8 Plasmodium berghei ANKA C57BL/6J anti-CD8 (early treatment) yes yes CM (100%) No CM Similar Prolonged survival (1-2 weeks) Yañez et al., 1996, J Immunol
CD8 Plasmodium berghei ANKA C57BL/6J anti-CD8 (early treatment) yes yes CM (67%) No CM Similar N.I. Yañez et al., 1999, Infect Immun
CD8 Plasmodium berghei ANKA C57BL/6J anti-CD8 (late treatment) yes yes CM (67%) CM (67%) Similar N.I. Yañez et al., 1999, Infect Immun
CD8 Plasmodium berghei K173 C57BL/6J anti-CD8 (early treatment) yes yes CM (91%) CM (8%) Similar N.I. Hermsen et al., 1997, Parasitology
CD8 Plasmodium berghei K173 C57BL/6J anti-CD8 (late treatment) yes yes CM (91%) CM (0-25%) Similar N.I. Hermsen et al., 1997, Parasitology
CD8 Plasmodium berghei K173 C57BL/10 anti-CD8 (early treatment) yes yes CM (75%) CM (25%) Similar N.I. Hermsen et al., 1997, Parasitology
CD8 Plasmodium berghei NK65 C57BL/6J anti-CD8 (late treatment) yes yes MA-ARDS (90%) Attenuated MA-ARDS N.I. ↓ lung weight, alveolar edema and cellular infiltration Van den Steen et al., 2010, Am J Crit Care Med
CD8 Plasmodium berghei NK65 CBA/JNCrj anti-CD8 yes yes N.I. N.I. Similar Prolonged survival (1-2 weeks) Waki et al., 1992, Immunology
CD8 Plasmodium berghei XAT CBA/JNCrj anti-CD8 no no N.I. N.I. Similar Resistant to P. berghei NK65 challenge infection Waki et al., 1992, Immunology
CD8 Plasmodium chabaudi chabaudi AS C57BL/6 anti-CD8 N.I. N.I. N.I. N.I. N.I. ↓ serum IFN-g Meding et al., 1990, Infect Immun
CD8 Plasmodium chabaudi chabaudi AS C57BL/6NCrlBR anti-CD8 no no N.I. N.I. Similar peak and developed 2 major recrudescences The 2 major recrudescendes coincided with the ↑ level of reticulocytosis, which returned to normal level when the parasites were cleared from the circulation Podoba et al., 1991, Infect Immun
CD8 Plasmodium chabaudi chabaudi AS C57BL/6 anti-CD8 no no N.I. N.I. Slightly increased peak Similar parasite-specific IgM and IgG Süss et al., 1988, Infect Immun
CD8 Plasmodium yoelii 17XNL C57BL/6 anti-CD8 no yes (~20%) N.I. N.I. N.I. N.I. Butler et al., 2012, Nat Immunol
CD8 Plasmodium yoelii 17XNL BALB/c anti-CD8 no no N.I. N.I. Similar N.I. Vinetz et al., 1990, J Immunol
CD8+ T cell/CD1d-restricted NKT cells Plasmodium berghei ANKA C57BL/6 b2 microglobuline -/- N.I. N.I. N.I. N.I. Similar on day 5 Prolonged survival (days) Nie et al., 2009, PLoS Pathog
CD8+ T cell/CD1d-restricted NKT cells Plasmodium berghei ANKA C57BL/6 b2 microglobuline -/- yes yes CM (94%) No CM N.I. N.I. Yañez et al., 1996, J Immunol
CD8+ T cell/CD1d-restricted NKT cells Plasmodium berghei K173 C57BL/6 b2 microglobuline -/- N.I. N.I. N.I. N.I. N.I. Plasma IFN-g and splenic IFN-g mRNA expression 24h p.i. was abrogated Mitchell et al., 2005, Infect Immun
CD8+ T cell/CD1d-restricted NKT cells Plasmodium berghei NK65 C57BL/6 b2 microglobuline -/- yes yes Liver pathology Liver pathology N.I. Similar liver injury, serum ALT levels, hepatic DX5+CD3+ cells; similar cytotoxicity by hepatic lymphocytes against hepatocytes Adachi et al., 2004, Int Immunol
CD8+ T cell/CD1d-restricted NKT cells/IP-10 Plasmodium berghei ANKA C57BL/6 b2 microglobuline -/- + anti-IP-10 N.I. N.I. N.I. N.I. Decreased on day 5 Prolonged survival (days) Nie et al., 2009, PLoS Pathog
CD80 Plasmodium chabaudi chabaudi AS NIH anti-CD80 no no N.I. N.I. Similar Similar IFN-g and IL-4 production by splenic T cells in vitro; similar IgG1 and similar IgG2a Taylor-Robinson et al., 1999, Immunology
CD80/CD86 Plasmodium chabaudi chabaudi AS NIH anti-CD80 and anti-CD86 no N.I. N.I. N.I. Decreased peak and developed a chronic, low parasitemia (~1%) ↑ IFN-g production by splenic T cells in vitro compared to anti-CD86 treatment alone, ↓ IL-4 production by splenic T cells in vitro; ↓ IgG1 Taylor-Robinson et al., 1999, Immunology
CD86 Plasmodium chabaudi chabaudi AS NIH anti-CD86 no N.I. N.I. N.I. Developed a chronic low parasitemia (~1%) ↑ IFN-g and abrogation of IL-4 production by splenic T cells in vitro; ↓ IgG1 and similar IgG2a Taylor-Robinson et al., 1999, Immunology
Class A type I and II macrophage scavenger receptors Plasmodium chabaudi AS C57BL/6 SR-AI/II -/- no no N.I. N.I. Similar Similar phagocytosis of pRBCs and free merozoites by peritoneal macrophages Su et al., 2002, J Infect Dis
COX-1/2 Plasmodium berghei ANKA ICR COX1/COX2 inhibitor (aspirin) yes yes CM (85%) CM (100%) Similar Slightly earlier death; similar mRNA expression of 5-lipoxygenase in brain and spleen; mRNA of phospholipase A2 similar in brain and ↑ on day 12 in spleen; mRNA expression of COX-1 and COX-2 was similar in spleen and ↓ in brain 7 days p.i.; ↑ serum leukotriene B4 levels Xiao et al., 1999, Am J Trop Med Hyg
COX-1/2 Plasmodium berghei K173 C57BL/6J non-selective COX-1/2 inhibitor (indomethacin) yes yes CM (58%) CM (62%) Similar N.I. Blok et al., 1992, J Infect Dis
COX-2 Plasmodium berghei ANKA CBA selective COX-2 inhibitor (celecoxib) yes yes CM CM Similar Earlier death (~days); earlier onset of cerebral symptoms (eg. edema, seizures);↓ bicycle-PGE2 level in brain (not in uninfected treated mice); similar brain mRNA expression of IL-10, 5-lipoxygenase and 5-lipoxygenase activating protein (FLAP) Ball et al., 2004, J Infect Dis
COX-2 Plasmodium berghei K173 CBA selective COX-2 inhibitor (celecoxib) yes yes HP&A HP&A Similar No induction of cerebral symptoms, similar progression of infection Ball et al., 2004, J Infect Dis
CRP Plasmodium berghei ANKA C57BL/6J CRP-tg yes N.I. CM (100%) No CM Decreased N.I. Aggrey et al., 2013, J Immunol
CRP Plasmodium yoelii C57BL/6J CRP-tg N.I. N.I. N.I. N.I. Decreased N.I. Aggrey et al., 2013, J Immunol
CTLA-4 Plasmodium berghei ANKA BALB/cAnNCrl anti-CTLA-4 yes yes CM (~30%) CM (100%) Similar ↑ numbers of CD8+ T cells in the brain; ↑ frequency of brain petechial hemorrhages; ↑ proportion of vessels plugged with iRBCs; ↑ numbers of pigmented (parasite-containing) macrophages in the liver; ↑ whole body, head and isolated brain parasite burdens (↑ bioluminescence of luciferase-expressing parasites); ↑ proportion of activated CD4+ and CD8+ T cells in the spleen; ↑ plasma IFN-g, TNF, IL-6, IL-10 and MCP-1/CCL2; ↑ secretion of IFN-g and IL-10 by stimulated CD4+ T cells and ↑ IFN-g secretion by stimulated CD8+ T cells; Hafalla et al., 2012, PLoS Pathog
CTLA-4 Plasmodium berghei ANKA C57BL/6 anti-CTLA-4 yes yes No CM CM (100%) Similar Earlier death (~2 weeks); ↑ weight loss; induction of neurological symptoms; no ↓ CD4+ T cells in spleen 5 days p.i.; ↑ spontaneous and anti-CD3 induced proliferation of spleen cells taken on day 5 p.i. But not from day 8 p.i.; similar IFN-g and ↑ NO production by anti-CD3 stimulated spleen cells 8 days p.i.; ↑ pathology and hemozoin deposition in liver Jacobs et al., 2002, J Immunol
CTLA-4 Plasmodium berghei ANKA C57BL/6 anti-CTLA-4 yes yes Moderate liver pathology ↑ Liver pathology Similar ↑ serum ALT and AST; ↑ weight loss; ↑ CD4+ and CD8+ T cells and similar gd T cells in liver parenchyma 8 days p.i.; ↑ and similar number of IFN-g producing cells in liver and spleen, respectively; similar and ↑ proliferation of liver and spleen cells, respectively Jacobs et al., 2004, Eur J Immunol
CTLA-4 Plasmodium yoelii 17XL BALB/c anti-CTLA-4 (day 0) 30% 70% N.I. Liver pathology Similar ↑ serum ALT and AST levels (↑ liver pathology); ↑ weight loss; ↑ % CD25+ CD4+, CD62Llow CD4+ and CD69+ CD4+ T cells in spleen; similar IL-12p40 and ↑ IFN-g, TNF-a, IL-4 and IL-10 in serum Lepenies et al., 2007, Microbes Infect
CTLA-4 Plasmodium yoelii 17XNL BALB/c anti-CTLA-4 (day 0) 20% 30% N.I. N.I. Decreased peak and earlier clearance Similar serum ALT and AST levels; similar body weight; ↑ % CD25+ CD4+, CD62Llow CD4+ and CD69+CD4+ T cells in spleen; similar IL-12p40 and TNF-a and ↑ IFN-g, IL-4 and IL-10 in serum Lepenies et al., 2007, Microbes Infect
CTLA-4/CD4 Plasmodium berghei ANKA BALB/cAnNCrl anti-CTLA-4 + anti-CD4 yes yes CM (~30%) CM (% depended on the time of administration) N.I. Early CD4 depletion delayed the onset of CM Hafalla et al., 2012, PLoS Pathog
CTLA-4/CD4 Plasmodium berghei ANKA C57BL/6 anti-CTLA-4 + anti-CD4 yes yes No CM No CM N.I. N.I. Jacobs et al., 2002, J Immunol
CTLA-4/CD8 Plasmodium berghei ANKA BALB/cAnNCrl anti-CTLA-4 + anti-CD8 yes yes CM (~30%) No CM N.I. N.I. Hafalla et al., 2012, PLoS Pathog
CTLA-4/IFN-g Plasmodium berghei ANKA BALB/cAnNCrl anti-CTLA-4 + anti-IFN-g yes yes CM (~30%) No CM N.I. N.I. Hafalla et al., 2012, PLoS Pathog
CTLA-4/TNF Plasmodium berghei ANKA BALB/cAnNCrl anti-CTLA-4 + anti-TNF yes yes CM (~30%) CM (~80%) N.I. N.I. Hafalla et al., 2012, PLoS Pathog
CXCL10 (IP-10) Plasmodium berghei ANKA C57BL/6 CXCL10 -/- 90% (at the end of observation day 20) 40% (at the end of observation day 20) CM (90%) CM (40%) N.I. N.I. Campanella et al., 2008, Proc Natl Acad Sci U S A
CXCL10 (IP-10) Plasmodium berghei ANKA C57BL/6 CXCL10 -/- yes 5% (at the end of observation day 20) CM (100%) CM (5%) Decreased Prolonged survival (at least until day 20); no neurological symptoms; ↓ blood vessels with intravascular inflammation; ↓ pRBC, CD4+ and CD8+ T cell sequestration (similar NK cells); similar ICAM-1+ blood vessels; ↑ parasite-specific proliferation and IFN-g production by CD4+ T cells; ↑ number of CXCR3+/IFN-g+CD4+ and CXCR3+/IFN-g+CD8+ T cells in spleen; ↓ IFN-g in serum; anti-IFN-g treatment had no effect on reduced parasitemia Nie et al., 2009, PLoS Pathog
CXCL10 (IP-10) Plasmodium berghei ANKA C57BL/6 anti-CXCL10 (d3-9) yes 20% (at the end of observation day 20) CM (100%) CM (20%) Decreased on day 5 Prolonged survival (at least until day 20); no neurological symptoms; ↓ blood vessels with intravascular inflammation; similar pRBC sequestration and ↓ CD4+ and CD8+ T cells (similar NK cells); majority of brain infiltrating T cells were CXCR3+ and CCR5-, indicating that other CXCR3 chemokines (MIG and I-TAC) can still recruit CXCR3+ T cells to the brain; similar expression of CD25 and CD69 activation markers in brain sequestering T cells and cells could still migrate to recombinant IP-10 in a chemotaxis assay; ↑ parasite-specific proliferation of CD4+ T cells; similar number of CXCR3+/IFN-g+CD4+ and CXCR3+/IFN-g+CD8+ T cells in spleen Nie et al., 2009, PLoS Pathog
CXCL10 (IP-10) Plasmodium berghei ANKA C57BL/6 anti-CXCL10 (d5-9) yes 50% (at the end of observation day 17) CM (100%) CM (50%) N.I. Prolonged survival (at least until day 17); no neurological symptoms Nie et al., 2009, PLoS Pathog
CXCL12 (SDF-1a) Plasmodium berghei ANKA C57BL/6 SDF-1a N.I. N.I. N.I. N.I. Decreased N.I. Garnica et al., 2002, Immunol lett
CXCL12 (SDF-1a) Plasmodium berghei ANKA BALB/c SDF-1a N.I. N.I. N.I. N.I. Decreased N.I. Garnica et al., 2002, Immunol lett
CXCL12 (SDF-1a) Plasmodium berghei ANKA BALB/c SDF-1a N.I. N.I. N.I. N.I. Decreased Similar number of CD11c+ cells in the bone marrow 14 days p.i.; ↑ numbers of cd11c+CD8a+ and CD11c+CD11b+ cells in the spleen 14 days p.i.; induction of periarteriolar CD11c clustering in the spleen Garnica et al., 2005, Immunology
CXCL4 (PF-4) Plasmodium berghei ANKA C57BL/6 PF-4 -/- 70% (at the end of observation day 10) 30% (at the end of observation day 10) CM (70%) CM (30%) Similar No neurological symptoms; no ↑ plasma TNF-a or IFN-g 5 days p.i.; no ↑ CXCR3 expression by splenocyt-derived T cells; no↑ number of CD4+ or CD8+ T cells in brain Srivastava et al., 2008, Cell Host Microbe
CXCL4 (PF-4) Plasmodium berghei ANKA PF4 -/- rPF-4 30% (at the end of observation day 10) 80% (at the end of observation day 10) CM (30%) CM (80%) Similar N.I. Srivastava et al., 2008, Cell Host Microbe
CXCL4 (PF-4) Plasmodium berghei ANKA C57BL/6 PF-4 -/- N.I. N.I. N.I. N.I. N.I. ↓ KLF4 expression in monocytes; ↓ monocytes in brain during CM Srivastava et al., 2010, PLoS ONE
CXCL9 (MIG) Plasmodium berghei ANKA C57BL/6 CXCL9 -/- 90% (at the end of observation day 20) 40% (at the end of observation day 20) CM (90%) CM (40%) N.I. N.I. Campanella et al., 2008, Proc Natl Acad Sci U S A
CXCR3 Plasmodium berghei ANKA C57BL/6 CXCR3 -/- 90% (at the end of observation day 23) 10-30% (at the end of observation day 23) CM (90%) CM (10-30%) Similar Prolonged survival (1–3 weeks); no neurological symptoms; ↓ CD8+ T cells and NK cells and similar NKT cells in the brain; ↓ CXCL9 (MIG), CXCL10 (IP-10), CCL5 (RANTES), CCL2 (MCP-1) and IFN-g expression in the brain Campanella et al., 2008, Proc Natl Acad Sci U S A
CXCR3 Plasmodium berghei ANKA CXCR3 -/- adoptive transfer of in vivo activated WT splenocytes or CD8+ T cells (day 0) 30% (at the end of observation day 20) 70-90% (at the end of observation day 20) CM (30%) CM (70-90%) N.I. ↑ number of WT (adoptively transferred) and CXCR3 -/- (own) CD8+ T cells in brain at the CM stage; ↑ IP-10, MIG, RANTES, MCP-1 and IFN-g mRNA expression in brain (similar to WT mice) Campanella et al., 2008, Proc Natl Acad Sci U S A
CXCR3 Plasmodium berghei ANKA C57BL/6 in vitro activated WT and CXCR3 -/- effector CD8+ T cells (day 5) yes yes CM CM N.I. Similar number of WT and CXCR3 -/- cells in spleen and ↓ number of CXCR3 -/- cells in brain after competitive (co)transfer in WT mice Campanella et al., 2008, Proc Natl Acad Sci U S A
CXCR3 Plasmodium berghei ANKA C57BL/6 CXCR3 -/- yes yes CM (100%) CM (32%) Similar Prolonged survival (1–3 weeks); no neurological symptoms or recovered from neurological symptoms; ↓ CXCL9 (MIG), CXCL10 (IP-10) and CCL5 (RANTES) mRNA expression in the brain; ↓ sequestered CD8+ T cells and CD4+ T cells, similar NK, NKT and CD11b+ cells in the brain; ↓ IP-10, perforin, FasL, IFN-g and LT-a and similar ICAM-1 mRNA expression in the brain; similar IFN-g mRNA expression in the spleen Miu et al., 2008, J Immunol
CXCR3 Plasmodium berghei ANKA CXCR3 -/- adoptive transfer of in vivo activated WT splenocytes or CD8+ T cells (day 0) yes yes CM (100%) CM (70%) N.I. N.I. Miu et al., 2008, J Immunol
CXCR3 Plasmodium berghei ANKA C57BL/6 CXCR3 -/- 70% (at the end of observation day 10) no (at the end of observation day 10) CM (70%) None (at the end of observation day 10) N.I. No neurological symptoms; no ↑ plasma TNF-a or IFN-g 5 days p.i.; no↑ number of CD4+ or CD8+ T cells in brain Srivastava et al., 2008, Cell Host Microbe
CXCR4 Plasmodium chabaudi chabaudi CR C57BL/6 CXCR4 antagonist N.I. N.I. N.I. N.I. Increased recrudescences N.I. Garnica et al., 2002, Immunol lett
Cystamine (CysH) Plasmodium chabaudi chabaudi AS A/J + cystamine hydrochloride (prophylactic treatment) yes (100%) ♂ yes (~60%); ♀ yes (~25%) N.I. N.I. Decreased N.I. Min-Oo et al., 2010, Exp Parasitol
Cysteamine (CysH) Plasmodium chabaudi chabaudi AS C57BL/6 + cysteamine hydrochloride No No N.I. N.I. Decreased on days 5-7 Antimalarial effect is less strong compared to known antimalarial drugs Min-Oo et al., 2010, Antimicrob Agents Chemother
Cysteamine (CysH) Plasmodium chabaudi chabaudi AS C57BL/6 + cysteamine hydrochloride + a suboptimal dose of artesunate No No N.I. N.I. Delayed onset and decreased peak, no recrudescences Synergistic antimalarial effect; ↓ disease symptoms Min-Oo et al., 2010, Antimicrob Agents Chemother
Cysteamine (CysH) Plasmodium chabaudi chabaudi AS A/J + cysteamine hydrochloride + a suboptimal dose of artesunate or dihydroartemisinin yes No N.I. N.I. Delayed onset and decreased Dose-dependent synergistic antimalarial effect; dose-dependent effect on survival; ↓ disease symptoms Min-Oo et al., 2010, Antimicrob Agents Chemother
Cysteamine (CysH) Plasmodium chabaudi chabaudi AS A/J + cysteamine hydrochloride (therapeutic treatment) ♂ yes (100%); ♀ yes (35%) ♂ yes (33-65%); ♀ yes (65-0%) N.I. N.I. Delayed onset and decreased The antimalarial effect and the effect on survival deminished when the onset of treatment was delayed; delayed ↑ of serum IFN-g and CCL2 (MCP-1) levels, ↓ serum CCL5 (RANTES) levels on d7 p.i., and similar serum levels of TNF, CCL4 (MIP-1b) and IL-10 Min-Oo et al., 2010, Exp Parasitol
Cysteamine (CysH) Plasmodium chabaudi chabaudi AS A/J + cysteamine hydrochloride (prophylactic treatment) yes (100%) yes (20%) N.I. N.I. Delayed onset and decreased Dose-dependent antimalarial effect; dose-dependent effect on survival Min-Oo et al., 2010, Exp Parasitol
Cytidine deaminase AID (Aicda)/Ig heavy chain µ-secretory domein Plasmodium yoelii 17XNL C57BL/6 Aicda -/- (mature B cells which produce IgM, but they cannot undergo isotype switching or secrete Abs) no yes (100%) N.I. N.I. N.I. Therapeutic blockade of PD-L1 and LAG-3 did not improve parasite clearance Butler et al., 2012, Nat Immunol
EPO Plasmodium berghei ANKA C57BL/6 rHuEpo yes yes CM less CM N.I. Improved survival; reversed clinical symptoms of CM; reduced brain hypoxia Hempel et al., 2011, Am J Pathol
EPO Plasmodium berghei ANKA CBA/J rHuEpo yes yes CM (93%) CM (40%) Similar Similar body weight loss and anemia; ↓ number of ring hemorrhages in the brain; ↓ and delayed TNF and IFN-g and similar caspase-3, caspase-8, TNFR1, TNFR2 and IFN-gR mRNA expression in the brain; similar blood NO levels Kaiser et al., 2006, J Infect Dis
EPO Plasmodium berghei ANKA C57BL/6J rHuEpo yes % depended on the time and dose of administration CM (93%) CM (% depended on the time and dose of administration) Similar ↑ packed cell volume levels; recovered from hypothermia at the time point when untreated mice succumbed; ↓ IL-1b, TNF, IFN-g and similar caspase-1, caspase-3 and LT mRNA expression in the brain; ↓ number of apoptotic neurons in the brain Wiese et al., 2008, Malar J
EPO Plasmodium chabaudi AS C57BL/6 anti-hEpo no yes (~70%) N.I. SMA (~70%) Similar Prolonged severe anemia; delayed induction of reticulocytosis Chang et al., 2004, J Infect Dis
EPO Plasmodium chabaudi AS A/J rmEpo yes yes SMA (100%) SMA (100%) Similar Similar anemia Chang et al., 2004, J Infect Dis

Pages

CSV